Hepcidin-guided screen-and-treat for iron-deficiency anaemia in young children
Authors: Haddy Tunkara-Bah
Journal: The Lancet Global Health (2022)

Anaemia is one of leading health problems among children in The Gambia.1Bojang KA Milligan PJM Conway DJ et al.Prevention of recurrence of anaemia in Gambian children following discharge from hospital.PLoS One. 2010; 5e11227Crossref Scopus (13) Google Scholar Previous analysis suggests that the prevalence of anaemia among children in The Gambia will increase by approximately 1·2% between 2017 and 2025.2Nyoni T Nyoni S Arima forecasting of the prevalence of anemia in children in the Gambia.EJARE. 2020; 1: 1-5Google Scholar In The Lancet Global Health, Rita Wegmüller and colleagues3Wegmüller R Bah A Kendall L et al.Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial.Lancet Glob Health. 2023; 11: e105-e116Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar report the results of a individually randomised, three-arm, double-blind, non-inferiority trial. The aim of the study was to test two hepcidin-guided screen-and-treat regimens designed to reduce overall iron dosage by targeting administration to periods when the children were safe and ready to receive iron supplementation. Participants were randomly assigned (1:1:1) to the WHO recommended regimen of one sachet of multiple micronutrient powder (MMP) daily containing 12·0 mg iron as encapsulated ferrous fumarate (control group); to MMP with 12·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 μg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 μg/L (12 mg screen-and-treat group); or to MMP with 6·0 mg per day iron for the next 7 days if plasma hepcidin concentration was less than 5·5 μg/L, or to MMP without iron for the next 7 days if plasma hepcidin concentration was at least 5·5 μg/L (6 mg screen-and-treat group). This study is highly relevant among participants in The Gambia. According to WHO recommendations, children aged 6–23 months in areas with a high prevalence of anaemia should receive 10·0–12·5 mg iron per day for 6 months.4WHOWHO guideline: use of multiple micronutrient powders for point-of-use fortication of foods consumed by infants and young children aged 6–23 months and children aged 2–12 years. World Health Organization, Geneva2016Google Scholar However, results from previous randomised trials of iron supplementation with iron-containing micronutrients powder have shown that the efficacy of this intervention was modest.5Tam E Keats EC Rind F Das JK Bhutta ZA Micronutrient supplementation and fortification interventions on health and development outcomes among children under-five in low- and middle-income countries: a systematic review and meta analysis.Nutrients. 2020; 12: 289Crossref PubMed Scopus (90) Google Scholar These findings might be due to poor compliance or poor absorption of iron. Studies have shown that high plasma hepcidin concentrations block intestinal iron absorption and macrophage iron recycling, causing iron restricted erythropoiesis and anaemia.6Pagani A Nai A Silvestri L Camaschella C Hepcidin and anemia: a tight relationship.Front Physiol. 2019; 101294Crossref Scopus (106) Google Scholar These findings suggests that hepcidin concentrations might be used to guide oral iron supplementation dosage. However, in the trial by Wegmüller and colleagues, compared with the control group, both screen-and-treat regimens were significantly less efficacious at improving haemoglobin concentrations (–5·6 g/L [98·3% CI –9·9 to –1·3] in the 12 mg screen-and-treat group and –7·8 g/L [98·3% CI –12·2 to –3·5] in the 6 mg screen-and-treat group) and neither regimen met the preset non-inferiority margin of –5 g/L. The results of this study add to the literature, indicating that the 6 mg screen-and-treat regimen would not be acceptable under any circumstance and even if the 12 mg screen-and-treat regimen is used it might only be suitable for long-term supplementation to achieve a gradual resolution of anaemia. Despite the strengths of the trial by Wegmüller and colleagues, it had some limitations. The study was done in a resource-limited settings (specifically in rural communities in The Gambia), but the authors did not discuss how to make the intervention feasible in areas where materials for laboratory tests are scarce and medical treatment is often based solely on clinical presentations. The authors did not describe how they managed participants with iron deficiency anaemia who had persistently high hepcidin concentrations due to infection, hepcidin-producing adenomas, or thalassemia syndromes.7Nemeth E Ganz T The role of hepcidin in iron metabolism.Acta Haematol. 2009; 122: 78-86Crossref PubMed Scopus (432) Google Scholar The findings indicate that despite the physiological effects of hepcidin concentration on iron absorption, its usage as a guide to oral supplementation dosage in children might be problematic due to some possible mediating factors—eg, in cases of chronic infection and inflammatory diseases in children, high doses of iron salts can alter the mechanism of hepcidin-mediated regulation of iron absorption in enterocytes. The key finding from this study is that hepcidin-guided screen-and-treat approaches are inferior to universal iron distribution in practice despite high adherence among children. Therefore, there is need to conduct more research for more effective strategies to combat anaemia in children in low-income settings with high exposure to pathogens. I declare no competing interests. Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trialThe hepcidin-guided screen-and-treat strategy to target iron administration succeeded in reducing overall iron dosage, but was considerably less efficacious at increasing haemoglobin and combating iron deficiency and anaemia than was WHO's standard of care, and showed no differences in morbidity or safety outcomes. Full-Text PDF Open Access